Purpose: :
The complement system of age-related macular degeneration (AMD)patients is marginally but chronically over-activated. Retinalpigment epithelial (RPE) cells and photoreceptor cells undergocell death during the development of this potentially blindingeye disease. In this study the balance between the pro-angiogenicvascular endothelial growth factor (VEGF) and the anti-angiogenicpigment epithelium-derived factor (PEDF) by RPE cells in responseto complement serum was analysed.

Methods: :
Increasing concentrations of complement competent human serumwere incubated with human RPE cells. Controls with the additionof zymosan to activate the complement cascade, zymosan alone,and heat-treated serum with inoperative complement were included.The secretion of VEGF and PEDF was measured by sandwich ELISA.Immunocytochemistry was performed for the in situ detectionof VEGF and PEDF. The experiments were supplemented by RT-PCRexpression analysis and Western Blot detection of both antagonists.

Results: :
Human complement competent serum stimulated the RPE cells toproduce enhanced amounts of VEGF while unspecific stimuli showedno influence on the secretion of VEGF. The combination of complementcompetent serum and zymosan was revealed as the most effectivetreatment for an increased VEGF production. The PEDF-specificstaining of RPE cells decreased with augmented concentrationsof complement competent serum. PCR data showed an enhanced amountof VEGF-encoding transcripts and an unaltered or lower amountof PEDF-specific transcripts. Western Blots confirmed the shiftin favour of VEGF when compared to PEDF after complement treatmentof RPE cells.

Conclusions: :
Activated complement may shift the balance between VEGF andPEDF produced by RPE cells towards the blood vessel chemoattractantVEGF. This finding may reveal a mechanism how enhanced complementactivation might contribute to a pro-angiogenic retinal environmentsupporting neovascularisation during the late stage of exsudativeAMD.